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Biomedical subjects

Natesa G Pandian

Publications and source records attributed to Natesa G Pandian.

At least 19 recordsLinked to original sources

Relation between high-density lipoprotein cholesterol and peripheral vasomotor function.

Low levels of high-density lipoprotein (HDL) cholesterol are one of the most common lipid abnormalities in patients with coronary artery disease. Endothelial dysfunction is also highly prevalent in patients with coronary artery disease. We sought to determine whether HDL cholesterol levels are correlated with endothelium-dependent vasomotion in patients being evaluated for atherosclerosis. Peripheral vascular endothelial function was assessed by high-resolution brachial artery ultrasound. Flow-mediated dilation (FMD) during reactive hyperemia was defined as the percent change in arterial diameter following 5-minute arterial occlusion. All patients underwent stress testing with nuclear single-photon emission computed tomographic imaging to determine percent left ventricular ejection fraction and define the presence or absence of coronary artery disease. One hundred fifty-one subjects (87 men, 64 women) were enrolled (average age 58 +/- 11 years). Total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were 188 +/- 48, 47 +/- 13, 108 +/- 37 and 154 +/- 88 mg/dl, respectively. The mean FMD for the entire group was 9.9 +/- 5.2%. Subjects with an HDL cholesterol of <40 mg/dl (n = 39) had lower FMD (7.4 +/- 3.6%) compared with those with an HDL cholesterol >/=40 mg/dl (11.0 +/- 5.5%, p <0.001). There was a significant correlation between FMD and HDL cholesterol level (linear regression, p <0.001), and in multivariate analysis, HDL cholesterol was an independent predictor of FMD. Peripheral endothelial function was abnormal in subjects with low HDL cholesterol and well-preserved in those with high HDL cholesterol. These data suggest that impaired endothelial function associated with low HDL cholesterol may be an additional, previously unrecognized mechanism contributing to the increased risk of atherosclerosis in these patients.

Age Factors↗

Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude.

BACKGROUND: Abnormalities in pulse wave amplitude (PWA) have been described in subjects with atherosclerosis and may be a marker of future cardiac events. We evaluated the relationship between changes in PWA of the finger and peripheral endothelial function. METHODS: We performed measurements of PWA with a novel finger plethysmograph (peripheral arterial tonometry [PAT]) and compared the findings with a simultaneous noninvasive measurement of peripheral endothelial function with brachial artery ultrasound scanning (BAUS) in 89 subjects. The PAT hyperemia ratio was defined as the ratio of PWA during reactive hyperemia relative to the baseline. Flow-mediated dilation (FMD) was defined by BAUS as the ratio of the brachial artery diameter during reactive hyperemia relative to the baseline. Sixty-eight subjects underwent exercise myocardial perfusion imaging (ExMPI). RESULTS: Fifty-four men and 35 women were examined. There was a linear relationship between the PAT hyperemia ratio and FMD during the same episode of reactive hyperemia (r = 0.55, P <.0001). Subjects in the lowest FMD quartile had the lowest PAT hyperemia ratio, whereas subjects in the highest FMD quartile had the highest PAT hyperemia ratio (P <.001 for trend). Similar to BAUS, the PAT hyperemia ratio was more impaired in subjects with cardiovascular risk factors and in subjects with ExMPI studies that were indicative of coronary artery disease. CONCLUSIONS: Assessment of PWA with PAT demonstrates patterns of abnormality similar to that of BAUS assessment of FMD. PWA during reactive hyperemia is influenced by factors known to affect endothelial function, including cardiovascular risk factors and coronary artery disease. These findings support the concept that analysis of PWA with PAT during reactive hyperemia may be used to study peripheral vascular endothelial function.

Blood Pressure↗

Tissue Doppler analysis is hindered in abnormal wall motion and changes in afterload.

BACKGROUND: Tissue Doppler (TD) analysis is used to estimate contractility. However, interference with hemodynamics has not been investigated. OBJECTIVE: To evaluate the effect of hemodynamic conditions and wall motion abnormalities on TD indices. METHODS: TD indices were obtained in 16 dogs and correlated with hemodynamics and wall thickening. RESULTS: An inverse relation between TD indices and systemic vascular resistance was observed when afterload-related parameters were included in the analysis (early systolic subendocardial velocity: r((multiple regression))=0.82, P<0.0001 vs. r((simple regression))=0.57, P=0.0002). Early systolic TD data were more closely related to hemodynamics than those derived from the entire systole. TD data did not correspond to the hyperkinesia of the contralateral wall in myocardial infarction, whereas the increase of gradient parameters reflected hypercontractility (P<0.05). CONCLUSION: TD indices are directly related to contractility and inversely to afterload. They do not reflect wall motion of those segments not involved in regional ischemia.

Animals↗

Effects of angiotensin II receptor blockade versus angiotensin-converting-enzyme inhibition on ventricular remodelling following myocardial infarction in the mouse.

Left ventricular (LV) remodelling following myocardial infarction (MI) is associated with increased morbidity and mortality. Previous data suggest that angiotensin II (Ang II) plays a central role in the molecular events contributing to LV remodelling. We explored the effects of angiotensin-converting-enzyme (ACE) inhibition versus Ang II (AT(1)) receptor blockade on LV remodelling in mice post-MI. Mice underwent sham procedure or left coronary artery ligation, and received placebo, the AT(1) receptor antagonist, losartan or the ACE inhibitor, enalapril. At 6 weeks, echocardiography and haemodynamic studies were performed. Infarct size and interstitial collagen content were determined. Expression of genes encoding atrial natriuretic peptide (ANP), collagen type I, AT(1a) and AT(1b) receptors were measured. The placebo MI group showed increased LV end-diastolic diameter, LV end-systolic diameter with depressed fractional shortening ( P <0.01 versus shams), increased LV mass and volume (both P <0.01 versus shams). The placebo MI group also exhibited increased non-infarct zone collagen content ( P <0.01), ANP ( P <0.01) and collagen type 1 ( P <0.01) gene expression, with a non-significant rise in AT(1a) receptor gene expression. Neither losartan or enalapril prevented LV dilation or improved fractional shortening. Both similarly lowered systolic blood pressure ( P <0.01 for each versus placebo). Losartan and enalapril inhibited LV hypertrophy ( P <0.01), and decreased ANP ( P <0.01) and collagen type 1 gene expression ( P <0.05). Levels of AT(1a) receptor gene expression were higher than shams ( P <0.05 for both), but similar to placebo. AT(1b) receptor gene expression was much lower than that for AT(1a) receptor and similar in all groups. Thus, in this model, AT(1) receptor antagonism and ACE inhibition have equivalent inhibitory effects on myocardial hypertrophy and fibrosis. These results serve as an important basis for planned investigations to evaluate the anti-remodelling effects of these agents on mice in which genetic manipulations are used to disrupt components of the Ang II signalling system.

Angiotensin Receptor Antagonists↗

Automated external defibrillator arrhythmia detection in a model of cardiac arrest due to commotio cordis.

INTRODUCTION: Cardiac arrest due to chest wall blows (commotio cordis) has been reported with increasing frequency in children, and only about 15% of victims survive. Automated external defibrillators (AEDs) have been shown to be life saving in adults with cardiac arrest, but data on their use in children are limited. In a swine model of commotio cordis designed to be most relevant to young children, we assessed the efficacy of a commercially available AED for recognition and termination of ventricular fibrillation. METHODS AND RESULTS: Ventricular fibrillation was produced in anesthetized juvenile swine by precordial impact from a baseball under controlled conditions. Animals were randomized to defibrillation after 1, 2, 4, or 6 minutes of ventricular fibrillation. Twenty-six swine underwent 50 ventricular fibrillation inductions. Sensitivity of the AED for recognition of ventricular fibrillation was 98%, and specificity for nonshockable episodes was 100%. All episodes of ventricular fibrillation were successfully terminated by the AED. CONCLUSION: In this experimental model of commotio cordis, the AED proved to be highly sensitive and specific for recognition of ventricular fibrillation and effective in terminating the arrhythmia and restoring sinus rhythm. These findings suggest that early defibrillation with the AED could save young lives on the athletic field.

Animals↗

Role of echocardiography in the diagnosis and treatment of patients with aortic stenosis.

PURPOSE OF REVIEW: Echocardiographic assessment plays a major role in the evaluation of aortic stenosis (AS). Because of its proven accuracy, ease of applicability, and safety, it is replacing cardiac catheterization for the assessment of AS in many centers. RECENT FINDINGS: In this review, we discuss the basic principles of echocardiographic assessment of AS and clinically challenging scenarios including AS with low cardiac output state or other structural heart disease. Dobutamine stress echocardiography is a useful tool for assessing low cardiac output AS. The role of transesophageal echocardiography in the evaluation of AS is also reviewed. SUMMARY: Echocardiographic techniques provide critical information in the assessment of patients with known or suspected AS and guide decision-making regarding the appropriateness of valve replacement.

Aortic Valve↗

Is the mitral valve area flow-dependent in mitral stenosis? A dobutamine stress echocardiographic study.

OBJECTIVES: The purpose of this study was to compare the effect of changes in flow rate on the mitral valve area (MVA) derived from two-dimensional echocardiographic planimetry and Doppler pressure half-time (PHT) methods in patients with mitral stenosis (MS). BACKGROUND: Dobutamine stress echocardiography has been proposed as a means of assessing the severity of MS. However, data regarding the effect of an increase in flow rate on MVA are limited. If MVA is indeed flow-dependent, this has important implications for the assessment of the severity of MS, particularly in the setting of reduced cardiac output (CO). METHODS: Dobutamine echocardiography was performed in 57 patients with isolated MS who were in sinus rhythm. The MVA was determined by planimetry and Doppler PHT methods. RESULTS: Cardiac output increased by > or =50% in 27 patients (group I) and by <50% in 30 patients (group II). In group I, the MVA by planimetry increased by only 10.6 +/- 2% and the MVA by PHT increased by 21.9 +/- 4.8%. These changes were similar to those observed in group II (10.7 +/- 3% and 14.8 +/- 4%, respectively; p = NS), despite a much smaller increase in CO. A clinically important change (from the severe to mild category) occurred in only one patient when using the PHT method and in none by planimetry. CONCLUSIONS: Changes in flow rate result in small but clinically insignificant changes in echocardiographic MVA measurement. These methods provide an accurate assessment of MS severity in a majority of patients, independent of changes in flow rate.

Adolescent↗

Therapeutic ultrasound in cardiology.

Ultrasound can be exploited to derive therapeutic results by using its bioeffects such as creation of mechanical vibrations, localized cavitations, microstream formation, physicochemical changes and thermal energy. Extensive in vitro and animal investigations during the last 2 decades have laid a foundation for ultrasound energy to be used for treatment purposes in various medical specialties. In the area of cardiovascular diseases, ultrasound could be used for thrombolysis, adjunct to coronary interventions, drug delivery, local gene transfer, and creating therapeutic lesions. The dispensation approaches to therapeutic ultrasound are varied, from the use of low- to medium-range frequency, low to focused high intensity, and catheter-based to external devices. Catheter-based ultrasound could be useful for intracoronary thrombolysis, and external ultrasound instrument with transcutaneous delivery could be of use in applications such as creation of myocardial lesions, peripheral vessel thrombolysis, and drug and gene delivery. Adjunct administration of microbubbles has been found to enhance thrombolysis, and drug and gene therapy. Ongoing studies strongly suggest that therapeutic ultrasound could have an important role in cardiovascular disorders associated with thrombosis, inflammation, atherosclerotic disease, and arrhythmias.

Animals↗

Myocardial perfusion imaging using contrast echocardiography.

BACKGROUND: Intense work during the last two decades has brought forth the use of myocardial contrast echocardiography to the clinical threshold for the diagnosis and evaluation of coronary artery disease. CLINICAL USE: A number of ultrasound contrast agents have been developed that act as red blood cell tracers and display myocardial perfusion when imaged by dedicated ultrasound imaging modalities. A considerable amount of experimental and clinical research has shown that myocardial contrast echocardiography can aid in the recognition of acute and chronic myocardial infarction, viable myocardium, and functionally significant coronary stenoses. Comparison of this technique to nuclear imaging and coronary arteriography has demonstrated excellent diagnostic accuracy in the evaluation of various coronary syndromes. Optimal practice of perfusion imaging requires a thorough knowledge of microbubble characteristics and imaging modalities, as well as good experience in the method. PERSPECTIVES: The technique continues to evolve from intermittent gated examination to real-time perfusion imaging that allows evaluation of both perfusion and functional parameters. The opportunity to target sites of pathology with specially engineered microbubbles could also aid in many therapeutic applications besides diagnostic imaging.

Animals↗

Recent role of imaging in the diagnosis of pericardial disease.

Noninvasive cardiac imaging techniques have made a striking impact on the evaluation and management of pericardial disorders. Two-dimensional and Doppler echocardiography are the methods of choice in the evaluation of pericardial effusion and cardiac tamponade. Magnetic resonance imaging, computed tomography, and transesophageal echocardiography are valuable in the assessment of pericardial thickness in suspected cases of constrictive pericarditis. Filling dysfunction associated with constrictive pericarditis is well demonstrated by Doppler flow velocity recordings of intracardiac flow jets, and pulmonary and hepatic venous flow streams. Tissue Doppler echocardiography, by which tissue velocity of myocardial regions and mitral annulus are analyzed, offers additional information in the differentiation of constrictive pericarditis and restrictive cardiomyopathy. Magnetic resonance imaging and computed tomography are the techniques of choice in the recognition of unusual disorders such as pericardial cysts, tumors invading the pericardium, and congenital absence of pericardium. Noninvasive imaging aids not only in the diagnosis of pericardial diseases, but also in the guidance of optimal therapy.

Blood Flow Velocity↗

Postoperative cardiac tamponade in the modern surgical era.

BACKGROUND: Pericardial effusions resulting in cardiac tamponade (CT) are uncommon after open heart surgery (OHS) and are associated with significant morbidity and mortality. Characteristics and outcomes of patients who develop postoperative CT are poorly defined. Our objective was to further analyze the population at risk for developing postoperative CT, identify potential perioperative and surgical risk factors, and evaluate the impact of CT on patient outcomes. METHODS: A retrospective analysis of 4,561 consecutive patients undergoing OHS at our institution was performed. Patients with clinical suspicion of pericardial effusion following surgery were evaluated by transthoracic or transesophageal echocardiography, and clinical parameters were analyzed. RESULTS: Forty-eight (1%) of the 4,561 patients were found to have echocardiographic evidence of a moderate or large pericardial effusion, of whom 36 (74%) had evidence of CT. The mean age of the patients with CT was 61 years. Coronary artery bypass grafting (CABG) had been performed in 24% of these patients, valve +/- CABG in 73%, and other OHS procedures in 3%. The incidence of CT following CABG alone was 0.2%, whereas it was 0.6% after valve +/- CABG. Females had a higher risk for developing CT, and this occurred earlier in the postoperative period when compared with men. Aspirin, heparin, or warfarin were given to 84% of patients within 3 days of surgery. Mean time to diagnosis of CT was 10 +/- 1 days after OHS. Prior to diagnosis of CT, the maximum international normalized ratio (INR) and partial thromboplastin time (PTT) were 2.7 +/- 0.3 and 68 +/- 5 seconds, respectively. Forty-nine percent of pericardial effusions were posterior and 46% were circumferential; one-third of the effusions were considered large by echocardiography. There was one in-hospital cardiovascular death. CONCLUSIONS: CT after OHS is more common following valve surgery than CABG alone and may be related to the preoperative use of anticoagulants. Females appear to be at higher risk for developing early postoperative CT. When diagnosed and treated promptly, postoperative CT should not significantly increase mortality.

Cardiac Surgical Procedures↗

The relationship between left ventricular shape and QT interval dispersion.

Left ventricular geometry is suspected to affect heterogeneity of myocardial repolarization; therefore, it is plausible but unproven that increased sphericity of the left ventricle is associated with greater QT interval dispersion. In 60 patients with dilated cardiomyopathy with left ventricular ejection fraction < or = 30%, we found that spherical distortion of the left ventricle was associated with increased QT dispersion, implying increased heterogeneity of myocardial repolarization.

Aged↗

Intraoperative epicardial coronary artery imaging: rationale, methods, and applications.

Epicardial coronary imaging using high frequency (7-12 MHz) ultrasound probes could aid the surgeon performing coronary artery bypass procedures by localizing the coronary artery segments underneath epicardial fat, identifying the site of coronary stenosis to be bypassed, evaluating the integrity of distal coronary artery, assessing the efficacy of anastomosis, and detecting anastomotic complications. While an ideal coronary imaging probe is yet to be developed, early clinical experience with vascular imaging probes applied on the coronary vessels suggests that epicardial coronary artery imaging could enhance the optimum performance of coronary interventions. Fabrication of a flexible high frequency probe that could be applied not only on the arteries on the anterior surface of the heart but also on the lateral and posterior surfaces could facilitate development of newer surgical procedures as well.

Arteries↗

A novel mechanism for the beneficial vascular effects of high-density lipoprotein cholesterol: enhanced vasorelaxation and increased endothelial nitric oxide synthase expression.

BACKGROUND: Low levels of high-density lipoprotein (HDL) cholesterol increase the risk of coronary artery disease (CAD), and recent clinical studies suggest that interventions in low-HDL patients are beneficial. The purpose of this study was to examine the effect of increased HDL levels on endothelium-dependent vasodilation. METHODS: We studied patients with CAD with a low-density lipoprotein (LDL) level of <100 mg/dL. Patients with an HDL level of < or =36 mg/dL were treated with niacin (n = 11), and patients with an HDL level of >36 mg/dL were followed as controls (n = 10). Baseline and 3-month follow-up studies of flow-mediated dilation (FMD) and blood lipid levels were obtained. RESULTS: HDL levels increased from 30.1 +/- 1.2 to 40.5 +/- 1.2 mg/dL in the niacin-treated patients (P <.001) but remained unchanged in the control patients. At baseline, FMD was impaired in both the treated (6.5% +/- 1%) and the control (7.3% +/- 1%) patients compared with 10 healthy subjects (16% +/- 2%, P <.01). After 3 months, FMD improved in the niacin-treated patients (11.8% +/- 1%, P =.001) but remained unchanged in the control patients (6.2% +/- 1%). Exposure of cultured human vascular endothelial cells to HDL in vitro enhanced expression of endothelial nitric oxide synthase (eNOS), as shown by immunoblotting. CONCLUSIONS: In patients with CAD and well-controlled LDL levels, elevation of HDL with niacin improves endothelial function. HDL increases eNOS protein expression in cultured vascular endothelial cells. Taken together, these observations suggest that HDL-mediated increases in eNOS expression may contribute to the observed enhancement in vasorelaxation and thus support a previously unrecognized mechanism for the beneficial cardiovascular effects of HDL.

Case-Control Studies↗

Use of pulse wave and color flow Doppler echocardiography in mouse models of human disease.

The noninvasive assessment of cardiovascular physiology in mice is challenging because of their small size and extremely rapid heart rates. In this study, we sought to determine the feasibility and utility of pulse wave (PW) and color flow Doppler imaging techniques when applied to mouse models of cardiac remodeling. We performed transverse aortic banding, induced aortic insufficiency (AI), or sham procedures in wild-type mice. Animals were anesthetized and transthoracic echocardiography was performed, including PW and color flow Doppler imaging. In aortic banded mice, color flow Doppler imaging was used to identify flow around the aortic arch, and PW measurements were performed distal to the constriction. A high-velocity jet across the aortic constriction was detected in all 4 banded animals. Both modalities were applied to AI mice in which AI was detected in all 5 mice but in none of the 5 shams. Pulse wave and color flow Doppler imaging were also used to screen senescent mice for valve abnormalities; AI was detected in 3 of 20 and mitral regurgitation in 2 of 20. We demonstrate here that PW and color flow Doppler imaging techniques are useful in the evaluation of mouse models of cardiac remodeling. In addition, this study indicates that these modalities may be potentially useful to screen transgenic mice for valve abnormalities.

Animals↗

Evaluation of a new ultrasound contrast agent (AI-700) using two-dimensional and three-dimensional imaging during acute ischemia.

BACKGROUND: A new intravenous contrast agent, AI-700, was evaluated to determine whether a bolus injection could be used to detect myocardial perfusion abnormalities during acute ischemia by using 2-dimensional (2D) and 3-dimensional (3D) myocardial contrast echocardiography. METHODS: 2D MCE was performed in 14 closed-chest dogs during coronary occlusion by using both continuous and triggered gray scale harmonic imaging and triggered power Doppler imaging. 3D MCE (open-chest) and nuclear perfusion imaging were performed in 10 of the 14 dogs. Postmortem triphenyl tetrazolium chloride (TTC) staining was performed to verify infarction. RESULTS: Thirteen of the 14 dogs had infarct by TTC; all 10 that had nuclear imaging showed a perfusion defect. Of the 13 dogs that had infarction, perfusion defects were detected in all (13 of 13) by gray scale harmonic imaging (sensitivity = 100%), and in 11 of 13 by power Doppler imaging (sensitivity = 85%). All 10 dogs that had nuclear imaging showed perfusion defects by gray scale harmonic imaging (sensitivity = 100%) and 8 of 10 by power Doppler imaging (sensitivity = 80%). The perfusion defect size, derived from 3D imaging (25% +/- 12%) correlated well with that from nuclear imaging (24% +/- 12%) (y = 0.9x + 3.8, r = 0.96, mean difference = 1.3% +/- 2.6%). The perfusion defect mass by 3D (22 +/- 14 g) also correlated well with the infarct mass by TTC staining (24 +/- 16 g) (y = 0.8x + 2.9, r = 0.89, P <.001, mean difference = -2.8 +/- 7.6 g). CONCLUSION: After a single bolus of AI-700, both 2D and 3D MCE could accurately detect perfusion defects representing the area at risk of infarction during acute ischemia compared with nuclear imaging and predicted the size of infarction as verified by TTC staining.

Animals↗

Reduced risk of sudden death from chest wall blows (commotio cordis) with safety baseballs.

OBJECTIVES: In an experimental model of sudden death from baseball chest wall impact (commotio cordis), we sought to determine if sudden death by baseball impact could be reduced with safety baseballs. BACKGROUND: Sudden cardiac death can occur after chest wall impact with a baseball (commotio cordis). Whether softer-than-standard (safety) baseballs reduce the risk of sudden death is unresolved from the available human data. In a juvenile swine model, ventricular fibrillation (VF) has been shown to be induced reproducibly by precordial impact with a 30-mph baseball 10 to 30 ms before the T-wave peak, and this likelihood was reduced with the softest safety baseballs (T-balls). To further test whether safety baseballs would reduce the risk of sudden death at velocities more relevant to youth sports competition, we used our swine model of commotio cordis to test baseballs propelled at the 40-mph velocity commonly attained in that sport. METHODS: Forty animals received up to 3 chest wall impacts at 40 mph during the vulnerable period of repolarization for VF with 1 of 3 different safety baseballs of varying hardness, and also by a standard baseball. RESULTS: Safety baseballs propelled at 40 mph significantly reduced the risk for VF. The softest safety baseballs triggered VF in only 11% of impacts, compared with 19% and 22% with safety baseballs of intermediate hardness, and 69% with standard baseballs. CONCLUSION: In this experimental model of low-energy chest wall impact, safety baseballs reduced (but did not abolish) the risk of sudden cardiac death. More universal use of these safety baseballs may decrease the risk of sudden death on the playing field for young athletes.

Animals↗